https://scholars.lib.ntu.edu.tw/handle/123456789/205579
標題: | A Mutation in Cartilage Oligomeric Matrix Protein (Comp) Causes Early- Onset Osteoarthritis in a Large Kindred Study | 作者: | MU, SHU-CHI LIU, HWA-CHANG WU, JER-YUARN LEE, MING-TA MICHAEL CHOU, CHING-HENG CHEN, LIANG-KUANG CHEN, YUAN-TSONG |
關鍵字: | Early-onset osteoarthritis;COMP;genome-wide linkage;phenotype;pseudoachondroplasia (PSACH);multiple epiphyseal dysplasia (MED) | 公開日期: | 2011 | 卷: | v.75 | 期: | 5 | 起(迄)頁: | 575-583 | 來源出版物: | ANNALS OF HUMAN GENETICS | 摘要: | We performed a genome-wide linkage analysis to identify susceptibility loci in a large six-generation extended family previously reported with early-onset osteoarthritis ( OA) DNA sequencing was performed to investigate involvement of the COMP (Cartilage oligomeric matrix protein) gene in this family. The region covering D19S884, D19S226, and D19S 414 on chromosome 19p following genome-wide scan from 70 individuals of this kindred showed significant linkage, with a maximum point LOD (logarithm of the odds ratio) score of 2.51 at D19S226. Direct sequencing of the COMP gene, the most plausible candidate gene in the region, identified a c. 2152C > T substitution in exon 18 which resulted in a substitution of tryptophan for arginine at position 718 located in the C terminal globular domain of the gene product. A total of 26 individuals were identified with this mutation of which 21 affected individuals had the mutation, and the other five younger individuals (18.6 +/- 11.3 years of age) carried the mutation without symptoms. The results indicate that COMP is the disease susceptibility gene and the c.2152C > T mutation in exon 18 could cause early-onset OA phenotypes in this kindred, which is compatible with a previous report that this mutation also causes a mild form of multiple epiphyseal dysplasia (MED). |
URI: | http://ntur.lib.ntu.edu.tw//handle/246246/241755 |
顯示於: | 醫學系 |
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